New research shows that the Zika virus has two routes by which it can infect a developing fetus, depending on when during a pregnancy the infection occurs. It also shows an existing drug might be able to limit the damage wreaked by the virus.
The new study, by scientists at the University of California at San Francisco and the University of California at Berkeley, suggests that an antibiotic called duramycin seems to be able to block Zika’s ability to latch onto the cells it wants to affect.
“It was day and night. There was either infection or no infection, depending on how much drug you used,” Lenore Pereira, one of two contributing authors of the study, said in an interview.
The article was published in the journal Cell Host and Microbe.
Pereira is a professor of microbiology in UCSF’s department of cell and tissue biology. She is an expert on cytomegalovirus, another virus that can trigger microcephaly — a condition in which a newborn has an abnormally small head — when it infects a developing fetus. She partnered with Eva Harris, a virus expert at UC Berkeley, on the study.
The researchers wanted to look at whether Zika virus would grow in cells from human placentas. The goal was to figure out how the virus makes its way to the developing fetus when a woman becomes infected in pregnancy.
They found that in the first trimester, the developing cells of the placenta were highly vulnerable to the virus. Pereira said the surface of the placenta does not become infected. But the virus somehow passes through the surface to the cells inside.
“We don’t know why,” she told STAT. “I really cannot tell you why the virus gets across. I cannot tell you how it gets across.”
She and Harris — who is an expert on dengue virus, a close relative to Zika — suspect that previous exposure to dengue virus may predispose some women to be more at risk of having an affected pregnancy if they become infected with Zika. But Pereira stressed that’s still a theory. And it’s known that women who haven’t previously been infected with dengue can also give birth to an affected child if they contract Zika during pregnancy.
Researchers have seen a wide range of birth defects associated with the Zika virus, including problems in the babies’ cardiac, digestive, and genitourinary systems.
The new research suggests that once infected, the placenta is, in effect, feeding virus into the fetus’s blood system, which allows Zika to make its way to the developing fetal brain.
Later in pregnancy — during the second and third trimesters — the virus is able to infect the outer cells of the amniotic sac, which encases the developing fetus. They pass into the amniotic fluid, a development that leaves the fetus “floating in virus,” Pereira said.
In this latter circumstance, the virus likely enters the fetus through the skin and gets taken up into the fetal blood stream.
Infected cells produced higher levels of virus when infection occurred in midgestation than later in the pregnancy, Pereira said. She suggested the damage the virus does to a developing fetus would likely vary, depending on how long it is exposed to the virus.
Interestingly, the researchers did these experiments using two strains of Zika virus — the African strain, first found in Uganda in 1947, and a strain from the current Latin American outbreak, from Nicaragua.
Both viruses can infect the cells and tissues of the placenta and amniotic sac. But the researchers saw a difference between the two — a possible hint as to why Zika’s association with birth defects has only come to light recently.
“We also found that the epidemic strain [viruses] were more productive,” said Pereira. “In other words, they could make more virus than the old prototype strain from Africa.”
“We don’t know why, but we did find that.”
The types of cells that were infected all carry a protein called TIM1. Pereira said when she came to suspect this protein was important for Zika infection, she did a search of the scientific literature for it, discovering an article from late last year that said the antibiotic duramycin prevents dengue and West Nile viruses from attaching to cells.
Given that both are related to Zika, she and her colleagues ran some experiments to see if the drug was also active against Zika. It was — dramatically reducing the virus’s ability to infect cells and proliferate.
The drug would need to be tested in animal models to see whether what works in the test tube is also effective — and safe to use — in a living organism, Pereira noted.
Those studies will take some time, but perhaps less time than it will take to develop and license a Zika vaccine, she suggested.